Title

A Kinetic Study of the Pictet-Spengler Reaction for the Condensation of Tryptamine with Formaldehyde

Date of Award

1985

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Chemistry and Biochemistry

First Advisor

Kenneth McMurtrey

Advisor Department

Chemistry and Biochemistry

Abstract

The Pictet-Spengler reaction in its simplest form involves condensation of a (beta)-arylethylamine with a carbonyl compound yielding a cyclized product. The reaction is thought to be a special case of intramolecular Mannich reaction that is believed to follow the general mechanism: A + X (DBLHARR) I (--->) P where I represents a Schiff's base type intermediate. Kinetic parameters associated with the reaction were investigated by condensing tryptamine (A) with formaldehyde (X) under pseudo first-order and physiological conditions. The reaction was monitored using HPLC. Rate constants were determined for the disappearance of tryptamine and formation of 1,2,3,4-tetrahydro- (beta)-carboline by examining the natural logarithm of peak height vs. time. The disappearance of tryptamine was found to follow a double exponential decay. Moreover, the presence of at least four distinct substances can be seen during the course of reaction. Two mechanisms that can give the observed decay are (1) A + X (DBLHARR) B (--->) P and (2) B (DBLHARR) A + X (--->) P. The former mechanism does not appear to satisfy kinetic data for the reaction, whereas the latter mechanism, specifically the mechanism A + X (DBLHARR) B; A + X (--->) C (DBLHARR) D, is consistent with kinetic data presently available. Data detailing kinetic parameters associated mechanistic implications of the reaction were discussed.